Effect of Dietary Supplementation on Body Composition, Pulmonary Function and Health-Related Quality of Life in Patients with Stable COPD

Background: Malnutrition is very common in patients with chronic obstructive pulmonary disease (COPD). Nutritional supplementation improves the patient’s nutritional status by increasing the energy intake and providing anti-inflammatory elements which can relieve the patient’s symptoms and delay the disease progression. This study sought to determine if energy and protein supplementation improves physical function, pulmonary function and health-related quality of life (HRQL) in stable COPD patients. Materials and Methods: The study was carried out in an outpatient setting on 60 stable COPD patients over a period of one year. Patients were randomized to intervention group (n=30), receiving supplemental nutrition in the form of additional protein and carbohydrates or control group (n=30), receiving only the usual standard diet. Lung function, body mass index (BMI), exercise capacity (6-minute walk test or 6MWT), mid-upper arm circumference (MUAC) and skin fold thickness (SFT) were evaluated, and clinical assessment was carried out at baseline and after completion of 12 weeks. The HRQL was assessed using Seattle obstructive lung disease questionnaire. Results: Twelve weeks of dietary supplementation resulted in a significant increase in weight and BMI of patients in the intervention group in comparison to the control group (P<0.005). Significant improvement was also observed in 6MWT and HRQL scores after nutritional intervention (P=0.002 and P=0.001, respectively). However, difference in MUAC, SFT and serum protein level after 12 weeks of follow up was not significant in any of the two groups. There was a similar degree of lung function improvement in both groups although it was not statistically significant. Conclusion: Nutritional supplementation with high protein and energy diet during 12 weeks of intervention improved body weight and composition, exercise capacity and quality of life in stable COPD patients.


INTRODUCTION
Chronic obstructive pulmonary disease is an important health problem across the globe. The disease is characterized by persistent airflow obstruction which is progressive resulting from inflammation and remodeling of the airways and lungs stimulated by exposure to toxins mainly due to a history of cigarette smoking (1). It has been recognized as the third leading cause of death and TANAFFOS continues to be the major cause of mortality and morbidity worldwide (2).
According to the World Health Organization consensus, 4.8% of the world population was diagnosed with COPD in 2010 (3). In 2005, more than 3 million people died of COPD accounting for 5% of all deaths globally and it is expected to become the third leading cause of death by 2030 (4). The current prevalence of COPD is not uniformly available in the Indian population. Although studies done by Murthy and Sastri (5) and Jindal (6). have reported the average prevalence rate of 5% in the adult population, higher rates have been reported in smokers, males, and rural areas.
Malnutrition is very common in patients with COPD.
Insufficient energy intake and systematic inflammation lead to malnutrition in these patients (7). Common clinical systemic manifestations are changes in body composition, metabolism and immune status which often lead to weight loss, dyspnea, fatigue, reduced exercise tolerance, poorer prognosis, increased susceptibility to infections and impaired quality of life independent of pulmonary function (8) .
Weight loss in COPD may be due to an increased energy expenditure imbalance caused by inadequate dietary intake which leads to reduction of diaphragmatic muscle mass and depressed diaphragm contractility (9).
Resting energy expenditure (REE), total daily energy needed, systemic inflammation and tissue hypoxia have been reported to be elevated in stable COPD patients and are considered to be a part of pathophysiologic mechanisms for weight loss (10,11). Patients with COPD experience gradual and progressive loss of skeletal muscle mass which not only affects their respiratory function but also causes muscle fatigue. This may further lead to reduction in exercise capacity and the ability to work (12).
Malnourished patients demonstrate more gas trapping, lower diffusing capacity and a reduced exercise performance than non-malnourished patients with similar pulmonary mechanics (13).
Several attempts have been made to find an association between malnutrition and impaired pulmonary function in patients with COPD (14)(15)(16). However, the exact causal relationship between malnutrition and COPD is difficult to establish and not clear yet. Malnutrition in COPD may be the consequence of worsened disease severity leading to compromised nutritional intake and reduced physical activity (muscle atrophy) and may alternatively be responsible for the wasting of muscles involved in breathing due to the progressive nature of COPD (17).
Malnourished COPD patients also have been reported to score worse than non-malnourished patients on a respiratory disease specific quality of life questionnaire (17,18).
The effect of nutritional support in malnourished patients has also been controversial. Several attempts have been made to reverse the weight loss and muscle wasting and improve respiratory and limb muscle function by administration of oral nutritional therapy (19)(20)(21) in stable COPD patients. However, several studies have also reported that nutritional intervention alone has little or no effect on improving pulmonary function parameters, functional exercise capacity and anthropometric characteristics (22)(23)(24).

Study Population
This was a prospective interventional study with 60 clinically stable patients of COPD attending chest clinic of our hospital.

Study design
A single-blind randomized, parallel group, design was used. After baseline assessment, the eligible patients were allotted by computer generated random numbers to one of the two groups and followed up for 12 weeks. A total of 65 patients were screened, out of which 60 patients were recruited and randomized into two groups of intervention and control (n=30 in each group). Those who were dropped out or in whom the investigations could not be completed were excluded leaving 3 and 2 patients, in intervention group and control group respectively.

Baseline evaluation:
Totally 60 patients were enrolled in the study and were evaluated prospectively with 30 patients in each group.

Post intervention evaluation:
There was a significant increase in weight and BMI of the patients in the intervention group but none in control group after 12 weeks of nutritional supplementation. In this study there were 12 patients in the study group and 18 patients in the control group with BMI < 18.5 Kg/m 2 meaning that 30 out of 60 patients were underweight i.e., incidence of malnutrition in this study was 50%.
The difference in the mean changes of studied parameters within and between the groups at the end of 8 weeks is shown in Table 3. The improvement in 6MWD and HRQL scores was found to be highly significant in the intervention group in comparison to the control group (P<0.05). The HRQL scores and 6MWD also increased after 12 weeks in the control group but failed to attain statistical significance. The differences observed in serum protein, MUAC and SFT between the groups after 12 weeks were not significant (Tables 3 and 4). Slight improvements were observed in the lung function parameters (FEV1, FVC, and FEV1/FVC) in both groups at the end of 12 weeks, although these changes were not statistically significant (Table 3). Also, independent t-test used to compare differences in lung function parameters post-supplementation vs pre-supplementation did not show a significant change between the groups at the end of the study period (Table 4).
The treatment was well tolerated and no adverse events were recorded. None of the patients had an acute exacerbation requiring emergency room treatment or hospitalization. There was no impact on lipid profile, liver function tests, renal function or blood pressure. The intervention group tolerated the high-protein, high-calorie diet without any complication. At the end of the study period, a significant difference between the study and control groups was observed in the 6MWT and HRQL (P< 0.05, Table 4). These parameters were also found to be positively correlated in response to nutritional supplementation at the end of the study (Table 5 and Figure 1).    Previously conducted studies have shown that approximately 25% of COPD patients may be malnourished and almost 50% of them admitted to the hospital had evidence of malnutrition advocating the fact that malnutrition remains a common problem in such patients (17,18). Studies have shown lean body mass depletion in COPD to be associated with an altered health status and increased mortality (28,29). It was also shown that muscle mass had strong impact on mortality in advanced COPD (30) . A review of nutritional intervention suggested to examine whether it is possible for depleted COPD patients to gain weight and rebuild muscle mass with adequate nutritional support (24). Otte et al. (31) reported that BMI served as a simple and accurate  Dollars approximately. Therefore, in the current study the total cost for the nutritional support per patient for the entire study duration was found to be approximately 120.00 Dollars.
Therefore, we confirm that cost-effectiveness of this intervention was efficient and that nutritional support in this study could be applied in clinical practice in India where incidence of malnutrition in COPD is quite high and most of the patients come from low socioeconomic background.
Our study had few limitations. Firstly, the sample size was small. A small difference between groups would not be detected as significant with small samples. A study with larger sample size and of longer duration of time to look into the benefits of nutritional intervention in underweight COPD patients is warranted.
Secondly, the nutritional intake was not standardized.